Age integration: conceptual and historical background.
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Biomedical subjects
Publications and source records attributed to J W Riley.
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A 64 year old caucasian male with known alcoholic liver disease presented with rectal bleeding. The patient bled repeatedly despite resuscitation. A sigmoid colectomy was performed following an angiogram. Large colonic, rectal and mesenteric variceal vessels were noted at surgery. Further bleeding postoperatively was rapidly controlled with octreotide infusion. Octreotide may be as useful in the control of colonic variceal bleeding as it is in the control of oesophageal variceal bleeding.
AIM: To assess the efficacy of cisapride therapy in relieving symptoms of functional dyspepsia. METHODS: After a 2-week placebo run-in period, 61 out of 74 patients were eligible to enter a 4-week double-blind treatment phase, consisting of treatment with cisapride (10 mg) or placebo tablets t.d.s. Gastric emptying was assessed scintigraphically at entry to the study. Patients were stratified before treatment into those with or without active chronic (Helicobacter pylori) gastritis. Patients were also classified retrospectively into those with 'reflux-like' dyspepsia (n = 29) and those with 'motility-like' dyspepsia (n = 32). RESULTS: At the end of the active treatment phase, there was a similar significant (P < 0.001) reduction in total symptom score from baseline in both cisapride (8.9 +/- 0.5 to 5.8 +/- 0.6) and placebo (9.7 +/- 0.6 to 5.5 +/- 0.6) groups. Scores for heartburn and continual bloating were significantly reduced in the cisapride but not the placebo group; improvement was attributable to patients with normal, rather than delayed, rates of gastric emptying. For continual bloating, significant improvement also occurred in the cisapride subgroup without gastritis, but not in the subgroup with gastritis (mean symptom score reduction 0.48 +/- 0.18, P = 0.03). For global evaluation by the investigator and by the patient, the overall improvement rates were not statistically different between cisapride and placebo groups. In those with normal gastric emptying, however, there was a significant (P = 0.01) improvement in general well-being in the cisapride but not in the placebo group. CONCLUSIONS: We were unable to show major differences in the short-term efficacy of cisapride and placebo in functional dyspepsia. There were indications, however, of beneficial effects of cisapride over placebo in those with 'reflux-like' dyspepsia, and in those without gastroparesis.
This research-based essay argues, as a stimulus to Forum discussion, that our currently age-differentiated society will give way to an age-integrated one. Age will lose its power to constrain people's entry, exit, and performance in such basic social institutions as education, work, and retirement. Revolutionary changes toward age integration are needed to reduce the "structural lag," in which the dynamism of human aging is outpacing the dynamism of structural change. To guide these changes, aging research is beginning to complement existing knowledge about human lives with new and deeper understanding of the social structures which shape and are shaped by these lives.
The relative contributions of altered gastric motor function and Helicobacter pylori-associated active chronic gastritis to the pathogenesis of functional dyspepsia are controversial. We therefore evaluated scintigraphically the intragastric distribution and gastric emptying of a mixed solid-liquid meal in 75 patients with functional dyspepsia; patients were subdivided on the basis of both specific symptom clusters and the presence or absence of H. pylori gastritis. Twenty-one (28%) patients displayed abnormal solid and/or liquid gastric emptying, with prolonged solid lag time the most prominent alteration detected. The number of patients with abnormal scintigraphic patterns increased to 36 (48%) when intragastric distribution parameters (fundal half-emptying time and antral maximal fraction) were examined. Although patients with reflux-like dyspepsia (N = 36) demonstrated significantly slower rates of liquid emptying at 45 and 70 min and a higher prevalence of abnormal liquid intragastric distribution when compared to patients with motility-like dyspepsia (N = 39) or to controls (N = 34), the absolute differences were small and unlikely to be of clinical significance. Patients without H. pylori gastritis (N = 50) demonstrated a significantly more prolonged solid lag time when compared to those with H. pylori gastritis (N = 25), but the difference was small and there were no other differences between these two subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)
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A 78-yr-old previously well caucasian female presented with a 6-wk history of profuse watery diarrhea and weight loss. Clinical investigation showed evidence of mild malabsorption. Multiple biopsies of colonic mucosa revealed a wide subepithelial band of collagen typical of collagenous colitis. Duodenal biopsies showed similar collagen deposition and partial villous atrophy. Some amelioration of symptoms occurred with sulfasalazine therapy. This is the first reported case of collagenous colitis with histological evidence of small intestinal involvement. At least in some patients, collagenous colitis and collagenous sprue appear to be manifestations of a single disease. For such cases, the term collagenous enterocolitis is suggested.
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Apolipoproteins B, A-I, and A-IV were localized in human intestinal epithelium using immunoperoxidase techniques. Staining was most obvious in villus tip cells. Lipid absorption resulted in an increase in intraepithelial staining for each apoprotein. The pattern for apo-B in the biopsy specimens taken after lipid absorption revealed a marked redistribution of staining to the intercellular spaces and an increase in the supranuclear staining of apo-A-I and apo-A-IV. After lipid absorption, staining appeared to extend further down the villus than in the fasting biopsy specimens. Quantitation of apo-A-I and apo-A-IV in isolated epithelial cells confirmed that the mass of these apoproteins increases in response to lipid absorption. Apolipoprotein B and apo-A-I were absent in the epithelium of 3 patients with abetalipoproteinemia while apo-A-IV was present in 2 patients. These studies demonstrate differences in the localization and quantitation of apoproteins in the villus-crypt unit as well as differences in the localization pattern of the different apoproteins.
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Lipid absorption is a complex process which involves coordinated gastric, intestinal, biliary and pancreatic function. Emulsification of dietary lipid occurs in the stomach and upper intestine where a series of enzymic events also occur. Phospholipids are digested by phospholipases. Colipase anchors lipase to the emulsion surface overcoming the interfering effect of bile salts. The products of lipolysis, monoglycerides and fatty acids, are removed from the emulsion surface by bile salts in the form of mixed micelles which transport lipid digestive products across the unstirred water layer to the epithelial cell. Within the intestinal epithelial cell a series of synthetic events occur resulting in the formation of chylomicrons and very low density lipoprotein (VLDL). Chylomicrons consists of an oily core of triglyceride surrounded by a membrane of phospholipids, free cholesterol and apoproteins which maintain the solubility of the particle in plasma. Chylomicrons from both experimental animals and man have specific apoproteins associated with them. These proteins include apoA-I, the major protein of plasma high density lipoproteins. During chylomicron metabolism, apoA-I and phospholipid from the chylomicron surface contribute to plasma high density lipoproteins. Other chylomicron apoproteins include apoB and apoA-IV, which are synthesized in the intestine, and apoC and apoE which are absorbed onto the chylomicron surface from other lipoproteins. The intestines also synthesizes, very low density sized particles (VLDL) while fasting and during lipid absorption. There is evidence that the intestine also synthesizes high density lipoproteins. The intestine has recently been recognized as a major site of synthesis of plasma lipoproteins and apoproteins, especially apoA-I for plasma high density lipoproteins.
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The role of the human intestine has been explored as a site of synthesis of apoA-IV, a major apoprotein of human intestinal triglyceride-rich lipoproteins. Intestinal biopsies were performed on normal volunteers while fasting and after lipid ingestion. Indirect immunofluorescence demonstrated a marked increase in immunofluorescence for apoA-IV during lipid absorption consistent with an increased intracellular content. ApoA-IV comprised 10-13% of chylomicron apoprotein and 24-30% of intestinal very low density lipoprotein (VLDL) as assessed by densitometry of sodium dodecyl sulfate gels of lipoproteins from chylous urine (mesenteric lymphatic-urinary fistula) and thoracic duct lymph (postoperative fistula). After one subject with chyluria ingested 40 g of corn oil, triglyceride excretion in urine was accompanied by an increased excretion of apoA-IV. 11.5 g of triglyceride and 81 mg of apoA-IV were recovered in the urine. In chylous urine 56% of apoA-IV was in the triglyceride-rich lipoproteins (chylomicrons and intestinal VLDL) and 44% in the d > 1.006-g/ml fraction. Normal plasma apoA-IV was 15.7+/-0.9 mg/dl (n = 14) whereas four subjects with abetalipoproteinemia had reduced levels 1.2, 7.6, 9.6, and 8.3 mg/dl, respectively. Lipid feeding in normal volunteers resulted in a rise in plasma apoA-IV (16.1+/-0.7 mg/dl to 18.5+/-0.7 mg/dl, n = 5, P < 0.01). In fasting plasma, 98% of apoA-IV was in the d > 1.21-g/ml fraction. In lipemic plasma, 10% of apoA-IV was associated with triglyceride-rich lipoproteins and 90% with the d > 1.21-g/ml fraction. Agarose column chromatography of fasting plasma confirmed that the bulk of plasma apoA-IV is free, unassociated with lipoproteins. These results demonstrate that apoA-IV is present in human intestinal epithelial cells and is secreted as a chylomicron and VLDL apoprotein. Within fasting plasma most of the apoA-IV is found free, unassociated with lipoproteins. After lipid ingestion apoA-IV is also found in plasma chylomicrons indicating that some apoA-IV remains associated with chylomicrons in plasma during chylomicron metabolism, although some may be transferred from the chylomicron surface.
Chronic cholesterol feeding has been shown to produce abnormal plasma lipoproteins in a variety of experimental animals and man. In order to explore the role of the intestine in the production of these abnormal lipoproteins, rats were chronically fed a diet containing 1% cholesterol and 10% olive oil and were compared to control animals, fed either normal chow or normal chow containing 10% olive oil. Mesenteric lymph lipoproteins from fasting lymph and from lymph obtained after acutely infusing cholesterol and olive oil were examined and compared to plasma lipoproteins from these animals. There were no differences in apoA-I output, cholesterol output, or distribution in lymph lipoproteins between the two groups of controls. The cholesterol-olive oil diet produced a mild hyperlipidemia (plasma cholesterol 81 --> 95 mg/dl, plasma triglyceride 95 --> 162 mg/dl). Plasma lipoprotein electrophoresis revealed an abnormal band with broad beta mobility and a reduction in HDL. Lipid analysis of ultracentrifugally separated fractions demonstrated the appearance of an intermediate density (1.006-1.030 g/ml) lipoprotein in plasma markedly enriched in cholesteryl esters. Analysis of fasting mesenteric lymph from chronically cholesterol-fed animals revealed similar apoA-I, cholesterol, and triglyceride outputs when compared to controls. Although in both groups most of the cholesterol was transported in d < 1.006 g/ml lipoproteins, there was a redistribution of cholesterol transport in d > 1.006 g/ml lipoproteins. In the chronically cholesterol-fed animals, 19% of fasting lymph cholesterol was transported in a lipoprotein of density 1.006-1.030 g/ml, compared to 4% in this density in controls. During the acute infusion of cholesterol and olive oil, the output of lymph apoA-I (226 +/- 20 versus 374 +/- 5 micro g/hr, P < 0.025) and lymph cholesterol (970 +/- 82 +/- 1774 micro g/hr, P < 0.01) was significantly lower in the chronically cholesterol-fed group, despite no significant change in triglyceride outputs (49 +/- 2 versus 58 +/- 7 mg/hr). Analysis of individual lymph lipoproteins from chronically cholesterol-fed animals revealed that significantly less apoA-I and cholesterol was carried in d < 1.006 g/ml lipoproteins than in controls. There was however, both a relative and absolute increase in the cholesterol and apoA-I content of intermediate and low density lymph subfractions. Particularly prominent in lymph from chronically cholesterol-fed animals was a lipoprotein (d 1.006-1.030 g/ml) which was inconsistently found in controls. This particle was rich in cholesterol and contained apoA-I. [(3)H]Retinol infusion studies revealed that this particle contained increased retinyl ester when compared to plasma, suggesting an intestinal origin. These results demonstrate that chronic cholesterol feeding in the rat results in altered mesenteric lymph lipoproteins which may contribute to the abnormalities found in plasma.-Riley, J. W., R. M. Glickman, P. H. R. Green, and A. R. Tall. The effect of chronic cholesterol feeding on intestinal lipoproteins in the rat.
The intestinal absorption of triglyceride constitutes a multistep process with active involvement of the pancreatobiliary system, the intestine and lymphatics. It is only through the integrated function of these organs that dietary triglyceride can be efficiently absorbed and delivered to the peripheral blood for subsequent metabolism. In this review we discuss each aspect of triglyceride absorption and chylomicron formation and illustrate how various diseases may interfere with the process resulting in fat malabsorption. In addition, the role of the intestine as a major synthetic source of lipoprotein constituents for circulating lipoproteins is discussed.
To study the metabolic fate of chylomicron phospholipid and apoproteins, 15 mg of doubly labeled ([(3)H]leu, [(32)P]phospholipid) rat mesenteric lymph chylomicrons were injected as an intravenous bolus into conscious rats. The specific radioactivity, composition, pool size, and morphology of the plasma lipoproteins were determined after 2-60 min. After injection of chylomicrons, there was a rapid transfer of radioactivity into high density lipoproteins (HDL). At peak specific activity in HDL (2-5 min), 35% of injected apoprotein and 25% of phospholipid radioactivity were recovered in HDL (d 1.063-1.21 g/ml), with smaller recoveries in other lipoproteins and liver. There was an initial rapid rise of (32)P specific activity in HDL and d 1.02-1.063 lipoproteins (low density lipoproteins [LDL]), but whereas LDL specific activity subsequently converged with that of d < 1.02 lipoproteins, HDL specific activity decayed more rapidly than LDL or d < 1.02 lipoproteins. Lipolysis of chylomicrons was associated with a transfer of phospholipid mass into LDL and HDL. At 5 min, 80% of injected triglyceride had been lipolyzed and there was a significant increase in phospholipid mass in LDL and a smaller increase in HDL. At 10 min, the mass of phospholipid in LDL had returned towards control values, and there was a further increase in phospholipid mass in HDL, which suggested phospholipid transfer from LDL to HDL. In donor lymph chylomicrons (3)H-radioactivity was present in apoprotein (apo)B, apoA-I, and apoA-IV, but only radioactivity of apoA-I and apoA-IV were transferred to HDL. Transfer of radioactivity was associated with loss of mass of apoA-I and apoA-IV from the fraction that contained the chylomicron remnants (d < 1.02). With injection of 15 mg chylomicron, there was a small but insignificant increase in the relatively large pool of HDL apoA-I. However, 60 min after injection of 250 mg of human or rat intestinal chylomicrons into the rat, there was a significant increase in HDL apoA-I that resulted from acquisition of a major fraction of the chylomicron apoA-I. After injection of chylomicrons, phospholipid vesicles were observed by negative stain electron microscopy in the LDL and HDL ultracentrifugal fractions, especially in the LDL. Upon addition of an osmotically active compound, cellobiose, vesicles were observed as flattened particles with a double lipid bilayer thickness ( congruent with 100 A). To validate further the identity of these particles, chylomicrons were injected into rats with [(3)H]glucose, and the recipient rats' plasma was fractionated by chromatography on 6% agarose. Trapping of [(3)H]glucose occurred in the void and LDL regions of the column, and vesicular particles were identified in these column fractions by negative stain electron microscopy. Catabolism of chylomicrons is associated with a rapid transfer of phospholipid, apoA-I, and possibly apoA-IV into HDL. Chylomicron phospholipid appears to give rise to vesicles which are probably incorporated into preexisting HDL. Chylomicron surface components may be an important source of plasma HDL.
A preliminary report of the use of ultrasonic scans to locate parathyroid tissue before neck exploration is presented. Three patients suffering from hyperparathyroidism had abnormal parathyroid tissue located before surgery. These findings were confirmed at operation. The role of ultrasonic scans of the neck before exploration is discussed.
A male, aged 60 with rheumatoid arthritis which was treated with prednisone, developed a severe symptomatic stomal gastritis at the site of a previous Polya partial gastrectomy. The endoscopic appearance of the lesion was similar to that of Candida infection, which is more frequently seen in the oesophagus. Candida albicans was cultured from biopsy specimens, and prompt resolution of the lesion and the patient's symptoms occurred with orally administered antifungal therapy. Primary gastric candidiasis should be considered in compromised patients with symptoms of infection of the upper part of gastrointestinal tract.